Ove Lundgren

Evaluation of laser Doppler flowmetry in the assessment of intestinal blood flow in cat.

Laser Doppler flowmetry with a differential detector system has been used in the assessment of blood flow in the feline small intestine. Simultaneous mucosal and serosal laser Doppler flowmeter recordings were compared with total blood flow of a bowel segment measured by an optical drop-recorder unit in 6 cats. Blood flow through the muscularis layer was estimated using the 85Kr washout technique. A correlation coefficient of r = 0.96 (mucosal recordings = 90, serosal recordings = 80, p less than 0.001) was obtained between laser Doppler flowmeter output signals and total blood flow at different levels of vascular tone, regardless of whether the flowmeter recordings were made from the mucosal or the serosal side of the bowel wall. At intense vasodilation, the flowmeters showed a tendency to underestimate blood flow. The flowmeter signals were at variance with the muscularis blood flow but were clearly correlated to the calculated mucosal-submucosal blood flow. The uneven blood flow distribution in the intestinal wall did not affect the ability of the flowmeters to reflect total blood flow from either side of the bowel wall. A calibration curve could be constructed for approximate interpretation of the laser Doppler signals in absolute flow units. However, further experiments in humans and further development of the technique must be performed to elucidate clinical applications of the method.

Pathogenesis of rotavirus diarrhea.

Abstract Rotavirus diarrhea is a major cause of infantile gastroenteritis worldwide. This review is mainly devoted to the effects of Rotavirus on intestinal epithelial transport and to the pathophysiological mechanisms proposed to underlie the intestinal fluid secretion caused by the virus.

5-Hydroxytryptamine and Cholera Secretion: Physiological and Pharmacological Studies in Cats and Rats

The intestinal secretion evoked by close intra-arterial infusion of 5-hydroxytryptamine (5-HT) in cats was inhibited by tetrodotoxin, a drug abolishing action potentials. Furthermore, the intestinal secretion produced by placing a 2-mM 5-HT solution in the intestinal lumen of rats was inhibited by hexamethonium, a ganglionic receptor-blocking agent. These observations strongly indicate that 5-HT-induced secretion is, at least in part, neurally mediated. It was also shown that 5-HT receptors are involved in the pathophysiology of choleraic secretion, since the secretion was inhibited by making the experimental animal tachyphylactic against 5-HT. No effects of 5-HT tachyphylaxis were noted on fluid transport in normal intestines. The results are discussed in relation to a new hypothesis for the pathophysiology of cholera secretion.

On the Role of Intramural Nerves in the Pathogenesis of Cholera Toxin-induced Intestinal Secretion

Intestinal secretion was produced in anesthetized cats and rats by exposing isolated intestinal segments to cholera enterotoxin. Giving, for example, tetrodotoxin, a nerve-conduction-blocking agent, or adding lidocaine, a local anesthetic agent, to the solution in the intestinal segments markedly inhibited the rate of choleraic secretion, and in most experiments a net absorption of fluid was observed. The results suggest that intramural nervous mechanisms are involved in the pathogenesis of choleraic secretion.

5-Hydroxytryptamine and cholera secretion: a histochemical and physiological study in cats.

The effect of cholera toxin on the content of 5-hydroxytryptamine (5-HT) in the enterochromaffin cells of the cat small intestine was estimated by cytofluorimetry of individual enterochromaffin cells at varying times after exposing the intestinal mucosa to the toxin. The observed changes in 5-HT levels in the enterochromaffin cells were correlated with the simultaneously measured rate of net fluid transport across the intestinal epithelium. Intestinal segments exposed to cholera toxin showed a statistically significant decrease in 5-HT levels of enterochromaffin cells compared with segments exposed to heat-inactivated cholera toxin. A good correlation (r = 0.73) was found between relative 5-HT fluorescence in enterochromaffin cells and net fluid transport across the intestinal epithelium. Thus, a diminished 5-HT content was associated with a decreased rate of fluid absorption or an increased rate of secretion. A hypothesis is presented for explaining the possible role of the enterochromaffin cells in the pathophysiology of cholera secretion.

Mucosal lesions in the human small intestine in shock.

Characteristic mucosal lesions in resected small intestinal segments from seven patients are reported. Preoperatively, four patients were in shock and general hypotension while the three remaining cases showed signs of local intestinal hypotension. The microscopic appearance of the mucosal lesions was in all patients identical with that previously observed in the feline and canine small intestine after haemorrhage or local intestinal hypotension. It is proposed that an extravascular short-circuiting of oxygen in the mucosal countercurrent exchanger and an intravascular aggregation of blood cells might produce tissue hypoxia which makes the mucosa vulnerable to enzymatic degradation.

Free radicals and pathogenesis during ischemia and reperfusion of the cat small intestine

BACKGROUND/AIM In spite of the interest in free radicals as mediators of ischemic damage, most information on these species in biological systems is derived from indirect measurements. Our aim was to obtain more direct information concerning sources of free radical production during ischemia and reperfusion. METHODS We have performed simultaneous measurement of radical generation, purine metabolites, reduced glutathione, neutrophil infiltration and morphological appearance in the cat small intestine in vivo during 60 minutes of ischemia followed by 60 minutes of reperfusion. RESULTS Radical formation increased abruptly on reperfusion and remained elevated in untreated animals. Inhibition by a monoclonal antibody (IB4) against the neutrophil and by allopurinol treatment was paralleled by improvement of biochemical and morphological parameters. The radicals detected during reperfusion could be divided into one component arising directly from the neutrophils, one due to the xanthine oxidase reaction, and one unknown source. CONCLUSIONS Neutrophils are a major source of radical production during reperfusion after ischemia. Radicals formed in the xanthine oxidase reaction seem to function as a primer for the neutrophils. The nonsignificant linear correlation between radical formation and morphological appearance suggests that factors other than free radicals are important for the development of intestinal damage after a period of ischemia.

Release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin.

During a four hour observation period vasoactive intestinal polypeptide (VIP) is released in increasing amounts from the feline small intestine exposed to cholera toxin. As VIP is known to be located almost exclusively in the intestinal nerves, the present findings strongly suggest that cholera toxin activates the enteric nervous system. The findings of this and other studies performed in this laboratory lead to the proposal that the choleraic secretion is, at least in part, secondary to the activation of intramural nervous reflexes in the gut.

Enteric nervous system

It is becoming increasingly evident that the nerves of mucosal surfaces may play an important role both during physiological and pathophysiological circumstances. This has, of course, been known for a long time with regard to the skin with its triple reponse. However, research performed during the last decade has shown that this is also true for mucosal membranes. In bronchial asthma, for example, nerves may play an important role in its pathophysiology, explaining the bronchial constriction, hypersecretion, and tissue edema associated with this disease (1). The mucosal lining of the gastrointestinal tract, including the biliary tract, is provided with an extensive nervous supply, the enteric nervous system (ENS). Although known for more than a century, its function has only recently been studied in any detail. This review will deal with our present knowledge of the physiology and pathophysiology of the ENS in the intestines and the gallbladder. The review is divided into two parts, the first being devoted to the intestines and a following one to the gallbladder.It is becoming increasingly evident that the nerves of mucosal surfaces may play an important role both during physiological and pathophysiological circumstances. This has, of course, been known for a long time with regard to the skin with its triple reponse. However, research performed during the last decade has shown that this is also true for mucosal membranes. In bronchial asthma, for example, nerves may play an important role in its pathophysiology, explaining the bronchial constriction, hypersecretion, and tissue edema associated with this disease (1). The mucosal lining of the gastrointestinal tract, including the biliary tract, is provided with an extensive nervous supply, the enteric nervous system (ENS). Although known for more than a century, its function has only recently been studied in any detail. This review will deal with our present knowledge of the physiology and pathophysiology of the ENS in the intestines and the gallbladder. The review is divided into two parts, the first being devoted to the intestines and a following one to the gallbladder.

Tissue Penetration and Measuring Depth of Laser Doppler Flowmetry in the Gastrointestinal Application

Tissue penetration of laser light and measuring depth (depth sensitivity) for laser Doppler flowmetry in the gastrointestinal application were studied in the feline and human bowel and stomach with a wall thickness of from 2.1 to 7.0 mm. Mucosal and serosal recordings from corresponding sites in the gastrointestinal tract were comparable and in the intestine correlated to total blood flow. Laser light was reflected by a mirror placed on the opposite side of the bowel wall, and hyperemic reactions were similarly recorded from both sides of the bowel with wall thickness up to 6 mm. Placing layers of unperfused feline small intestine (average thickness, 2.1 mm) between the probe and the perfused feline gastric wall attenuated the laser Doppler signal in an exponential manner. We conclude that with this instrument, the tissue penetration and measuring depth of laser Doppler flowmetry are at least 6 mm in the gastrointestinal application.